The primary theme of this proposal is the development of samarium (II) iodide (SmI2) as a selective reductive coupling agent for organic synthesis. New reactions to be explored will include the cyclization of acyl radicals and anions utilizing acyl selenide substrates and ketyl-allene cyclizations. Intramolecular conjugate addition reactions SmI2 will be added to he repertoire of SmI2-promoted reactions. Aryl, alkenyl, and secondary and tertiary alkyl radical cyclizations promoted by SmI2 will be examined. Nitriles will be explored as radical acceptors in SmI2- promoted cyclizations. The SmI2-promoted alpha-alkylation reaction of amines and ethers will be applied in cyclization reactions to generate nitrogen heterocycles and bicyclic ethers. The major focus of the proposal will be on sequencing organic reactions using SmI2 as a reducing agent. In fact one of the unique and most useful features of SmI2 is its ability to sustain a variety of sequential reactions in one pot processes. One subsection of this chemistry will involve the use of reductive fragmentation reactions as one component of the sequential processes. Reactions have been designed to allow reductive coupling reactions to precede fragmentation, and vice versa, Because SmI2 is formally a one electron reductive coupling reactions to precede fragmentation, and vice versa. Because SmI2 is formally a one electron reductant, both one- and two-electron processes can be promoted by this reagent in any combination or order, depending upon the design of the substrate. Thus serial radical reactions, radical reactions followed by anionic reactions, anionic reactions succeeded by radical reactions, and sequential anionic reactions all appear feasible and will be examined. Finally, we will examine various sequential reactions based upon the newly developed conjugate addition reactions. These will include conjugate addition/Claisen reactions, conjugate addition/aldol reactions, conjugate addition/ketyl-olefin coupling reactions, and conjugate addition reactions followed by nucleophilic acyl substitution reactions. The long term goal of the program is to develop more efficient and selective general methods for the synthesis of organic molecules that can be utilized by medicinal chemists, toxicologist, pharmacologists, and bioorganic chemists for the study of biologically active materials